A large segment of the population suffers from antigen-induced allergies. Typical allergic responses include rhinitis, urticaria, eczema, skin flushing, pruritus, angioedema and bronchoconstriction (asthma). A large number of preparations are available to persons suffering from such allergic symptoms which are useful in alleviating the symptoms described above. Desirable qualities for relief of such symptoms include effectiveness of relief, length of effective action and safety of active ingredient. However, most anti-allergic preparations cause undesirable side effects in many patients taking the medication, e.g., drowsiness, dry mouth, etc.
It is known that certain opioids can precipitate asthma attacks in sensitive patients, and that morphine and related opioids are to be avoided during asthma attacks due to inherent respiratory depressant activity. It is also known that morphine may cause pruritus in certain individuals, which may be related to the degranulation of mast cells. Degranulation of mast cells is believed to play a central role in causing allergic responses.
Bernstein and Swift (Arch. Dermatol., 155:1366, Nov. 1979) have shown that subcutaneous administration of the narcotic antagonist naloxone blocked pruritus caused by primary biliary cirrhosis. The same article showed that administering an enkephalin analog with opioid-like activity precipitated an asthma attack in one patient. Bernstein U.S. Pat. No. 4,181,726 discloses treatment of itching associated with Hodgkin's disease, mycosis fungoides, intractable pruritus and the like by injection of naloxone. Parenteral administration of naloxone for treating antigen-induced itch, asthma, urticaria and angioedema is similarly disclosed by Smitz et al., Ann. Intern. Med., 97(5): 788-90 (1982).
It is well recognized in the field of opiate agonism and antagonism that there are multiple opiate receptor sub-species, each receptor having its own particular affinity for narcotics and antagonists thereof. The presence of multiple receptors for opiates and antagonists thereof creates a general unpredictability in the structure-activity relationship for narcotics and narcotic antagonists, as described in Goodman and Gilman's The Pharmacological Basis of Therapeutics, 6th ed., the teachings of which are incorporated herein by reference.